ES2952207T3 - Methods to mimic chronic calorie restriction and to impart health benefits to an animal - Google Patents

Abstract

The invention provides methods for mimicking chronic calorie restriction to impart a health benefit in an animal or for using a partially restricted intermittent diet to impart a health benefit to an animal. Such methods may include feeding an animal two different diets that have different caloric contents in a specific ratio to achieve such benefits. (Automatic translation with Google Translate, without legal value)

Description

DESCRIPTION

Methods to mimic chronic calorie restriction and to impart health benefits to an animal

BACKGROUND OF THE INVENTION

field of invention

The invention relates generally to non-therapeutic methods and diets and kits for providing health benefits to an animal by mimicking chronic calorie restriction and using specific intermittent calorie restriction diets, and particularly to methods of using feeding patterns to provide such benefits. to health.

Description of the related technique

Chronic calorie restriction (CR) without malnutrition has been shown to improve both average and maximum life expectancy, promote healthy living (life free of chronic diseases), and prevent, delay or reduce the incidence of many chronic diseases. including cardiovascular diseases, cancer, diabetes, hypertension, stroke, dementia, Alzheimer's disease, Parkinson's disease. Unfortunately, it is very difficult to practice CR for the health benefits mentioned above due to the requirement to reduce daily caloric intake for life.

Furthermore, when managing an animal's weight, particularly promoting weight loss, it is a very common practice to reduce caloric intake by restricting the amount of food available to the animal on a chronic and daily basis. While chronic calorie restriction has been associated with numerous health benefits, challenges remain. For example, restricting daily food intake makes the animal chronically hungry. Hunger is an unpleasant state that often causes one or more unwanted behaviors on the part of the hungry animal, for example, begging, foraging, binge eating, and the like. Additionally, managing weight loss through chronic, daily calorie reduction can lead to undesirable outcomes that affect body composition. Animals that lose weight often lose both fat body mass and lean body mass and reduce their daily energy expenditure. The reduced daily energy expenditure caused by chronic daily caloric reduction during weight loss makes it easy for animals to regain lost weight and makes it very difficult for them to maintain their ideal body weight after weight loss. Therefore, when losing weight, it is often more desirable to lose excess fat body mass while preserving as much lean body mass as possible and maintaining a higher daily energy expenditure.

Various methods for mimicking CR are known in the art. For example, fasting every other day can improve life expectancy (Goodrick et al., Mech Aging Dev 1990;55:69 - 87). But fasting every other day for a lifetime is also very difficult to practice. Fasting for 4 consecutive days every two weeks can also increase longevity (Sogawa H, Kubo C. Mech Aging Dev 2000; 115: 61-71), but this approach is also very difficult for most people and animals. A fasting-mimicking diet (FMD) has been shown to reduce biomarkers and risk factors for aging, diabetes, cancer, and cardiovascular disease (Wei et al., Sci Transl. Med, 2017, 9: waai8700). FMD is low in calories, sugar and protein, but high in unsaturated fats. Additionally, people must take FMD five consecutive days a month for a minimum of three months to receive any benefits.

Methods for managing weight loss and body mass are known in the art. For example, US8158683 discloses the use of aronia extracts to promote weight loss. US8143215 discloses the promotion of weight loss by applying a composition that increases satiety or suppresses appetite comprising a flavoring on food. US7989009 discloses a method for promoting weight loss using black tea extract, white tea extract, guarana extract, oolong tea extract, green mate extract, thiamine, choline and N-acetylcysteine. US6204291 discloses a process for promoting weight loss in overweight dogs using L-carnitine. US7744930 discloses compositions, methods and kits for improving weight loss while inhibiting the loss of lean body mass using soy protein and chromium in salt or chelate form. US20040077556A1 discloses methods for promoting weight loss and lean muscle mass using epigallocatechin gallate, caffeine and l-tyrosine. US7850997 discloses methods for improving lean body mass and exercise performance using L-arginine alpha amino n-butyrate. US5804596 discloses a method of using forskohlin to promote lean body mass and treat mood disorders. US20070082026A1 discloses methods for reducing caloric intake and controlling weight using dietary fiber. US8226973 discloses the use of isoflavones to reduce body fat accumulation in male mammals. Document US20110281245A1 discloses a system for regulating caloric intake by managing food plates. Document US20100109876A1 discloses devices, systems and methods to control caloric intake by modifying consumer behavior. Document US20030072846A1 discloses packages useful for controlling dietary caloric intake. Document US20100126588A1 discloses a programmed intermittent automatic watering system for animals.

Additionally, US8968804 and US91073426 disclose methods for promoting weight loss and minimizing the loss of lean body mass by feeding the animal for a first period a first diet containing calories that meet the maintenance energy needs of the animal and feeding the animal during a second period on a second diet containing calories that do not meet the animal's maintenance energy requirements, where such periods may vary from days to weeks.

These methods are often at least partially effective in mimicking CR, controlling weight loss and/or lean body mass, and related conditions. However, these methods may not provide all the desired health benefits or provide adverse or very difficult conditions to practice. Therefore, there is a need for new methods to provide health benefits associated with chronic calorie restriction without the need to reduce caloric content on a daily basis.

SUMMARY OF THE INVENTION

A non-therapeutic method

animal, the method comprising: feeding the animal a caloric maintenance diet containing calories that meet the maintenance energy requirements of the animal during a caloric maintenance period; and feeding the animal a caloric reduction diet containing about 40% to about 60% of the calories contained in the caloric maintenance diet during a caloric reduction period, in which the caloric maintenance period and the period calorie reduction are in a ratio of approximately 4:3.

A non-therapeutic method of feeding an animal to impart a health benefit to the animal, the method comprising: feeding the animal a diet without limiting caloric intake during a period of ad libitum feeding; and feeding the animal a caloric reduction diet containing from about 40% to about 60% calories that meet the maintenance energy requirements of the animal during a period of caloric reduction; in which the ad libitum feeding period and the caloric reduction period are in a ratio of approximately 4:3.

A caloric maintenance diet containing calories that meet the maintenance energy requirements of an animal and a caloric reduction diet containing approximately 40% to approximately 60% of the calories contained in the caloric maintenance diet for use in a method of reducing the incidence of cancer, treating cancer, cancer prevention, reducing the incidence of cardiovascular diseases, treatment of cardiovascular diseases, prevention of cardiovascular diseases, prevention of type II diabetes, prevention of prediabetes, treatment of diabetes type I, treatment of type II diabetes or treatment of prediabetes, the method comprising: feeding the animal a caloric maintenance diet containing calories that meet the maintenance energy requirements of the animal during a caloric maintenance period; and feeding the animal the caloric reduction diet containing from about 40% to about 60% of the calories contained in the caloric maintenance diet during a caloric reduction period; in which the caloric maintenance period and the caloric reduction period are in a ratio of 4:3.

A kit defined by the claims, comprising a complete and balanced diet and a complete and balanced calorie reduction diet containing between 40% and 60% of calories that satisfy the maintenance reduction diet of an animal containing between a 40% and 60% calories. calories that meet the maintenance energy requirements of an animal for use in a method of reducing the incidence of cancer, treating cancer, preventing cancer, reducing the incidence of cardiovascular diseases, treating cardiovascular diseases, preventing cardiovascular diseases, preventing type II diabetes, prevent prediabetes, treat type I diabetes, treatment of type II diabetes, or treatment of prediabetes, comprising the method: feeding the animal with the diet without limit of caloric intake during a period of ad libitum feeding; and feeding the animal the caloric reduction diet containing from about 40% to about 60% of calories that meet the maintenance energy requirements of an animal during a period of caloric reduction; in which the ad libitum period and the caloric reduction period are in a ratio of approximately 4:3.

Other objects, features and advantages of the present invention will be readily apparent to those skilled in the art.

DETAILED DESCRIPTION OF THE INVENTION

Definitions

The term "animal" means a human or other animal that can benefit from one or more methods of promoting weight loss by an animal, promoting weight loss by an animal while preventing or minimizing mass loss lean body on the part of the animal, avoiding a reduction in energy. metabolism by an animal, reducing the risk of an animal regaining weight after weight loss, and improving undesirable animal behaviors associated with reduced caloric intake, including avian, bovine, canine, equine, feline, hyrcine, murine, ovine, and porcine animals.

The term "pet" means domestic animals such as cats, dogs, rabbits, guinea pigs, ferrets, hamsters, mice, gerbils, horses, cows, goats, sheep, donkeys, pigs and the like. In one aspect, companion animal may refer to a dog and/or a cat.

The term "intermittent period(s)" or "intermittently" means a first period and a second period of the same or different duration that repeat at defined intervals. For example, daily intermittent periods would involve performing one act during one day, performing a different act the next day, and possibly repeating the pattern for as many two-day periods as necessary or desirable. Similarly, one act, such as feeding an animal, could be performed for a week and a second act, such as feeding an animal a different diet, could be performed for two weeks, and the cycle would repeat for a year or for the entire the life of the animal. The same would apply for periods of multiple days, weeks, months, quarters, years and the like, for example, daily, every other day, every two three days, every two days four, every two days five days, every two days six, weekly, every two weeks, every two weeks, every two weeks, monthly, every two months, quarterly, annually and the like.

The term "jointly" means that an animal is fed, during a first period, with a first diet containing calories that satisfy the maintenance energy needs of the animal and is fed, during a second period, with a second diet containing calories that They do not meet the animal's maintenance needs. energy requirements according to the invention and the animal is administered a different compound, composition or other agent (1) together in the dietary composition or (2) separately at the same or different frequency using the same or different routes of administration at approximately the same time or periodically. "Periodically" means that the agent is administered on a dosage schedule acceptable for a specific agent and that the food is fed to an animal routinely as appropriate for the particular animal. "About the same time" generally means that the food and agent are administered at the same time or within approximately 72 hours of each other. "Conjointly" specifically includes administration schedules in which the agent is administered for a prescribed period and the dietary compositions of the invention are administered indefinitely.

The term "complete and balanced" when referring to a feed composition means a feed composition that contains all known required nutrients in appropriate amounts and proportions based on recommendations from recognized authorities in the field of animal nutrition, and therefore are capable of to serve as a sole source of dietary intake to maintain life or promote production, without the addition of supplemental nutritional sources. Nutritionally balanced pet food and animal feed compositions are widely known and widely used in the art, for example, complete and balanced food compositions formulated in accordance with standards established by the Association of American Feed Control Officials (AAFCO). ).

The term "single package" means that the components of a kit are physically associated in or with one or more containers and are considered a unit for manufacture, distribution, sale or use. Containers include, but are not limited to, bags, boxes, cartons, bottles, packages of any type, design or material, wrappers, shrink wrap, fixed components (e.g., stapled, attached or similar), or combinations thereof. A single package may be containers of individual dietary compositions of the invention physically associated so as to be considered a unit for manufacturing, distribution, sale or use.

The term "virtual package" means that the components of a kit are associated by instructions on one or more physical or virtual components of the kit that tell the user how to obtain the other components, for example, a bag or other container containing a component and instructions directing the user to go to a website, contact a recorded message or fax return service, view a visual message, or contact a caregiver or instructor for instructions on how to use the kit or information technical or safety on one or more components of a piece of equipment.

The term "about" means plus or minus 20%, preferably plus or minus 10%, more preferably plus or minus 5%, most preferably plus or minus 2%.

All percentages expressed herein are by weight or amount of the total weight or amount of the composition unless otherwise expressed.

The invention is not limited to the particular methodology, protocols and reagents described herein because they may vary. Furthermore, the terminology used herein is intended to describe particular embodiments only and is not intended to limit the scope of the present invention.

As used here, the singular form of a word includes the plural, and vice versa, unless the context clearly indicates otherwise. Therefore, the references "a", "an" and "the" generally include the plurals of the respective terms. Similarly, the words "comprises", "comprising" and "understanding" should be interpreted inclusively and not exclusively. Similarly, the terms "include", "including" and "or" should be interpreted as inclusive, unless such interpretation is clearly prohibited in the context. Similarly, the term "examples", particularly when followed by a list of terms, is merely exemplary and illustrative and should not be considered exclusive or complete. All embodiments using "comprises", "comprising" or "comprising" may be replaced by "consisting essentially of" or "consisting of".

Unless otherwise defined, all technical and scientific terms and any acronyms used herein have the same meanings as commonly understood by one skilled in the art in the field of the invention. Although any composition, method, article of manufacture or other means or materials similar or equivalent to those described herein may be used in the practice of the present invention, the compositions, methods, articles of manufacture or other means are described herein. or preferred materials.

The invention

The invention is defined by the claims. In one embodiment, a non-therapeutic method

Chronic caloric restriction to impart a health benefit in an animal comprises feeding the animal a caloric maintenance diet containing calories that meet the maintenance energy requirements of the animal during a caloric maintenance period and feeding the animal a caloric diet of maintenance. reduction diet containing about 40% to about 60% of the calories contained in the caloric maintenance diet during a caloric reduction period, where the caloric maintenance period and the caloric reduction period are in a ratio of about 4: 3.

In particular, the present inventor has unexpectedly discovered that animals fed a specific intermittent feeding pattern, a period ratio of 4:3, with a specific caloric reduction will mimic a chronic calorie restriction diet. For example, an animal may be fed a maintenance diet for a period of 4 days and a reduction diet for a period of 3 days. Generally, the reduction diet contains about 40% to about 60% of the calories contained in the caloric maintenance diet. In one aspect, the reduction diet may have around 50% of calories.

As such, through the present method, the animal may receive health benefits that include: preserving lean body mass, preventing or minimizing loss of lean body mass during the animal's weight loss, preventing a reduction in energy metabolism of the animal, reduce the risk of the animal regaining weight after weight loss, maintain ideal body weight, increase longevity, increase healthy life expectancy, maintain a healthy metabolism, maintain normal levels of glucose, lipids and cholesterol in the blood, reduce IGF-1 levels, maintain normal blood pressure, maintain normal brain function, promote healthy brain aging, promote skeletal muscle health, and improve undesirable animal behaviors associated with reduced caloric intake.

In another embodiment, a non-therapeutic method of feeding an animal to impart a health benefit comprises feeding the animal a diet without limiting caloric intake for an ad libitum period and feeding the animal a calorie-reducing diet containing approximately 40% to about 60% of calories meet the animal's maintenance energy requirements during a period of caloric reduction. The ad libitum period and the caloric reduction period are in a ratio of approximately 4:3. Additionally, in one embodiment, the ad libitum period and the caloric reduction period may be consecutive.

In particular, the present inventor has unexpectedly discovered that animals fed a specific intermittent feeding pattern, a period ratio of 4:3, with a specific caloric reduction will provide health benefits, such as benefits for weight loss and weight maintenance, without limiting calories during an ad libitum period. For example, an animal may be fed any diet for a period of 4 days and a reduction diet for a period of 3 days. Generally, the reduction diet contains about 40% to about 60% calories that meet the animal's maintenance energy requirements. In one aspect, the calorie reduction diet may contain approximately 50% of the calories necessary to meet the daily maintenance energy requirement of the animal. In another aspect, the reduction in caloric intake may be exclusively from reduced dietary carbohydrates.

While feeding during the caloric reduction period, the caloric maintenance period, and/or the ad libitum period as described may be sufficient, the present methods also include embodiments in which the feeding pattern is repeated for at least two cycles. , for several cycles, at most. as long as the animal benefits from the feeding pattern (for example, achieves a desired weight loss), or during the life of the animal.

Although the present methods contemplate the use of the present methods during any time cycle, such as 5 days, 7 days, 10 days, 14 days, etc., where, within the cycle, individual or ad libitum maintenance periods and periods of restrictions are in a ratio of 4:3, generally the caloric maintenance period or ad libitum period can be 4 days and the caloric reduction period can be 3 days. Furthermore, while individual feedings/days can be spread throughout the cycle in a non-consecutive manner, e.g. 1 week cycle with 2 days maintenance or ad libitum, then 2 days restricted, then 2 days maintenance or ad libitum, then 1 day restricted, generally the individual periods can be consecutive, e.g. 1 week cycle with 4 maintenance or ad libitum days, then 3 restricted days. As such, in one aspect, the 4 days and the 3 days may be consecutive and in another aspect, the 4 days and the 3 days may be non-consecutive.

As discussed herein, while the present intermittent diet may be for any amount of time and for any number of cycles, in one embodiment, feeding for the caloric maintenance period or the ad libitum period and feeding for the caloric reduction period are repeated for a combined period of at least 1 month. In one aspect, feeding for the caloric maintenance period or ad libitum period and feeding for the caloric reduction period may be repeated over a period of at least 6 months.

In one embodiment, the methods of the invention are implemented in conjunction with the administration of a weight loss agent or any other agent that provides a health benefit. Any such agent that is compatible with the feeding patterns of the invention can be used in the invention. In various embodiments, the agent may be carnitine, isoflavones, pyruvate, fish oil, DHA, EPA, fibers, calcium, resistant starch, medium chain triglycerides, green tea extract, phentermine, diethylpropion, orlistat, sibutramine, megestrol, phenylpropanolamine , oxandrolone, oleoylethanolamide, probiotics, ephedra, conjugated linoleic acid, glucomannan and mixtures thereof.

The methods described herein may be useful for monitoring weight loss and the related functions described herein for any animal. In one aspect, such methods may be directed toward companion animals, including those whose diet is controlled by an owner or caretaker. In a specific aspect, the animals may be dogs and/or cats.

Also discussed here are kits suitable for implementing the methods of the invention. The kits comprise in separate containers in a single package or in separate containers in a virtual package, as appropriate for the kit component, (1) a complete and balanced first food composition containing calories that meet the maintenance energy requirements of a animal; (2) a second complete and balanced food composition containing calories that do not meet the animal's maintenance energy requirements; and (3) instructions for using the feed compositions to at least one of promoting weight loss of an animal, promoting weight loss of an animal while preventing or minimizing loss of lean body mass of the animal, preventing a reduction in energy metabolism of an animal, reduce the risk of an animal regaining weight after weight loss, maintain ideal body weight, increase longevity, reduce the incidence of cancer, treat cancer, prevent cancer, reduce the incidence of cardiovascular diseases, treat cardiovascular diseases, prevent cardiovascular diseases, prevent type II diabetes, prevention of prediabetes, treatment of type I diabetes, treatment of type II diabetes, treatment of prediabetes, reducing levels of IGF-1 and improvement of undesirable animal behaviors associated with reduced caloric intake by feeding the animal for a first period with the first food composition and feeding the animal for a second period with the second food composition. The kits may further comprise one or more weight loss agents or other health agents.

Where the kit comprises a virtual package, the kit is limited to instructions in a virtual environment in combination with one or more physical components of the kit. Generally, the kit contains the food compositions and other physical components in quantities sufficient to implement the methods of the invention and the virtual package contains instructions related to the use of the physical components to implement the methods of the invention.

Also discussed herein is a means of communicating information or instructions for one or more of promoting weight loss by an animal, promoting weight loss by an animal while preventing or minimizing loss of lean body mass by part of the animal, prevents a reduction in energy metabolism by an animal, reduce the risk of an animal regaining weight after weight loss, maintain ideal body weight, increase longevity, reduce the incidence of cancer, treat cancer , prevent cancer, reduce the incidence of cardiovascular diseases, treat cardiovascular diseases, prevent cardiovascular diseases, prevent type II diabetes, prevention of prediabetes, treatment of type I diabetes, treatment of type II diabetes, treatment of prediabetes, reduction of IGF-1 levels and improvement of undesirable animal behaviors associated with reduced caloric intake by feeding the animal during the caloric maintenance period a caloric maintenance diet containing calories that meet the animal's maintenance energy requirements and feeding the animal during a period of caloric reduction with a caloric reduction diet containing calories that do not meet the animal's maintenance energy requirements and, optionally, a weight loss or other health-imparting agent. The medium comprises a document, a digital storage medium, an optical storage medium, an audio presentation, or a visual presentation containing the information or instructions. The media can be a website, a visual presentation, a brochure, a product label, a leaflet, an advertisement, a brochure, a public announcement, an audio tape, a video tape, a DVD, a CD -ROM, a computer readable chip, a computer-readable card, a computer-readable disk, computer memory, or a combination thereof, containing such information or instructions.

Useful information includes one or more of (1) recommended feeding programs for the animal, particularly based on the species and body condition of the animal (e.g., overweight or obese), (2) recommended weight loss agent or for health to be administered in conjunction with the use of the recommended feeding pattern, and (3) contact information for the animals or their caregivers to use if they have any questions about the invention and its use.

EXAMPLES

The invention may be further illustrated by the following examples, although it will be understood that these examples are included merely for illustrative purposes and are not intended to limit the scope of the invention unless specifically indicated otherwise.

Example 1

Eight-week-old rats were fed a high-fat diet to promote weight gain for 2 months, and then the rats were fed a standard AIN93M diet (Product D10012M available from Research Diets, Inc.) for 3 months. weeks to determine each rat's maintenance energy requirement (MER). The rats were randomly distributed into 11 groups. Rats were subjected to weight loss regimens to induce weight loss for 6 months as shown in Table 1 with one of the diets shown in Table 2.

Table 1

Table 2

The invention may be further illustrated by the following examples, although it will be understood that these examples are included merely for illustrative purposes and are not intended to limit the scope of the invention unless specifically indicated otherwise.

As shown in Table 1, the 11 groups were fed as follows.

Control group: Rats receiving the AIN-93M diet (Control) continued with the same feeding pattern for 6 months.

The 25% Calorie Restriction (CR) group was fed the 25% CR diet daily to meet 75% of the maintenance energy requirement (MER) for 6 months.

A once-weekly 25% intermittent calorie restriction group (6:1-25CR): Rats were fed 75% of their MER on one day with the 25% CR diet and 100% of their MER with the control diet for six days.

A twice-weekly 25 % intermittent calorie restriction group (5:2-25CR): Rats were fed 75% of their MER on two days with the 25% CR diet and 100% of their MER with the control diet for 5 days.

A group with 25% intermittent caloric restriction three per week (4:3-25CR): Rats were fed 75% of their MER for 3 days with the 25% CR diet and 100% of their MER with the control diet for 4 days.

A once-weekly 50% intermittent calorie restriction group (6:1-50CR): Rats were fed 50% of their MER one day with the 50% ICR diet and 100% of their MER with the control diet for six days.

A twice-weekly 50% intermittent calorie restriction group (5:2-50CR): Rats were fed 50% of their MER on two days with the 50% ICR diet and 100% of their MER with the control diet for 5 days.

A 50% intermittent calorie restriction group three per week (4:3-50CR): Rats were fed 50% of their MER for 3 days with the 50% ICR diet and 100% of their MER with the control diet for 4 days.

A once-weekly 75% intermittent calorie restriction group (6:1-75CR): Rats were fed 25% of their MER one day with the 75% ICR diet and 100% of their MER with the control diet for six days.

A twice-weekly 75% intermittent calorie restriction group (5:2-75CR): Rats were fed 25% of their MER on two days with the 75% ICR diet and 100% of their MER with the control diet for 5 days.

A three-per-week 75% intermittent calorie restriction group (4:3-75CR): Rats were fed 25% of their MER three days on the 75% ICR diet and 100% of their MER on the control diet for 4 days.

Rats were housed individually per cage, on a 12-h light/dark cycle, and given water ad libitum. Body composition was measured using the EchoMRI-700 Body Composition Analyzer (Echo Medical Systems, Houston, Texas). Blood (0.5 ml) was collected for measurements of biochemical parameters from rats in all groups at the end of the study. After 6 months of dietary intervention, after 12 h of overnight fasting, samples were taken, including blood collection (week 24), and tissue dissection and weighing were performed. Serum insulin (Mercodia, Uppsala, Sweden) and IGF-1 (R&D Systems, Minneapolis, USA) levels were quantified using rat ELISA kits. Serum glucose was determined using the TRUE Result™ Blood Glucose Meter (Florida, USA). Homeostatic model assessment (HOMA) was calculated using insulin and glucose values. The results are presented in Tables 3-5.

Table 3

*Diets are described using the following format (maintenance days): (restricted days)-(restricted percentage) as described in paragraphs [0037-47]

Table 4

*Diets are described using the following format (maintenance days): (restricted days)-(restricted percentage) as described in paragraphs [0037-47]

Table 5

*Diets are described using the following format (maintenance days): (restricted days)-(restricted percentage) as described in paragraphs [0037-47]

Tables 3-5 show that rats in the CR group significantly lost body weight and body fat compared to baseline and control (Tables 3-4). Furthermore, rats in the CR group had significantly lower fasting blood insulin and IGF-1 at the end of the study compared to the control group (Table 5).

Unexpectedly, all three intermittent fasting (IF) regimens (once a week, twice a week, and three times a week) with a 25% reduction from baseline MER failed to significantly reduce body weight and body fat compared to baseline and control (Tables 3-4). 4). These treatments also did not significantly reduce insulin and IGF-1 compared to the control (Table 5). These data show that 25% IF up to three days per week is not effective in mimicking the CR phenotype (lower body weight and body fat) and biomarkers (IGF-1 and insulin).

When IF was introduced with a 50% restriction from baseline MER, once weekly failed to reduce body weight and body fat compared to baseline and control (Tables 3-4). Furthermore, once-weekly 50% IF did not reduce insulin and IGF-1 compared to control (Table 3). Twice weekly 50% IF failed to significantly reduce body weight, but significantly reduced body fat compared to baseline and control (Tables 3-4). Twice weekly 50% IF failed to reduce IGF-1, but significantly reduced insulin compared to control. Three times a week 50% IF significantly reduced body weight and body fat compared to baseline and control (Tables 3-4) and significantly reduced insulin and IGF-1 compared to control (Table 5). In fact, three times a week IF (i.e., the 4:3-50CR) completely mimicked both the CR phenotype (lower body weight and body fat) and the biomarkers (insulin and IGF-1) by inducing the same degrees of changes. in those parameters than the CR.

When IF was introduced with a 75% restriction from baseline MER, once weekly failed to significantly reduce body weight and body fat compared to baseline and control (Tables 3-4). Furthermore, once-weekly IF did not reduce insulin and IGF-1 compared to control (Table 5). Twice weekly 75% IF significantly reduced body weight and body fat compared to baseline and control (Tables 3-4). Twice weekly, IF also significantly reduced IGF-1 and insulin compared to control (Table 5). But the reduction in body fat, insulin, and IGF-1 did not coincide with the reduction induced by CR, indicating that the 5:2-75CR regimen is not as effective as CR.

Three times a week 75% IF significantly reduced body weight and body fat compared to baseline and control (Tables 3-4) and significantly reduced insulin and IGF-1 compared to control (Table 5 ). IF three times a week (i.e., 4:3-75CR) induced lower body weight and body fat than CR, but the biomarkers (insulin and IGF-1) induced three times a week at 75% were compared with those induced by CR (Table 5). As such, 75% IF, although more restrictive than CR, does not provide better insulin or IGF-1.

In summary, 25% IF (up to three days per week) failed to mimic any CR phenotype or biomarker. Twice weekly IF at 75% partially mimicked the CR phenotype. Three days a week IF at 75% induced a more severe phenotype change than CR with comparable CR biomarkers. 50% IF at the frequency of 3 days per week completely mimics the CR phenotype and biomarkers.

Example 2

Five-month-old male C57BL6J mice were fed a high-fat diet (HFD, 45 t) for 5 months to develop obesity. After this feeding period, mice were separated into groups and fed diets based on percentages of MER using a standard AIN-93M diet (Product D 10012M available from Research Diets, Inc.) as described in Table 6.

Table 6

| ' ' '

'

Mice were housed individually per cage, on 12-h light/dark cycles, and given water ad libitum. Body composition was measured on day 1 and every 30 days using the EchoMRI-700 body composition analyzer (Echo Medical Systems, Houston, Texas). Samples were collected, after which homeostasis was confirmed by visual inspection.

After 6 months of dietary intervention, blood and tissue samples were collected after 12 h of overnight fasting, as well as final weight measurements. The resulting data is provided in Table 7.

Table 7

While both 4:3 ad lib regimens (IF2 and IF4) led to a much smaller reduction in both body weight and %body fat compared to traditional CR and the 4:3 maintenance regimens described above (IF1 and IF3), both IF2 and IF4 provided surprisingly greater weight loss and lean body mass reserve. On the other hand, 4:3 maintenance regimens (IF1 and IF3) mimic 100% CR.

Typical preferred embodiments of the invention have been described in the specification. Although specific terms are used, they are used only in a generic and descriptive sense and not for purposes of limitation. The scope of the invention is set forth in the claims. Obviously, many modifications and variations of the invention are possible in light of the above teachings.

Claims (15)

1. A non-therapeutic method therapeutic in an animal, wherein the nontherapeutic health benefit is selected from the group consisting of: preserving lean body mass, preventing or minimizing loss of lean body mass during weight loss by the animal, preventing a reduction in the animal's energy metabolism, reducing the risk of the animal regaining weight after weight loss, maintaining ideal body weight and improving undesirable animal behaviors associated with reduced caloric intake, the method comprising: feeding the animal a caloric maintenance diet containing calories that meet the animal's maintenance energy requirements during a caloric maintenance period; and feeding the animal a caloric reduction diet containing about 40% to about 60% of the calories contained in the caloric maintenance diet during a caloric reduction period; in which the caloric maintenance period and the caloric reduction period are in a ratio of approximately 4:3. 2. A kit comprising in separate containers in a single package or in separate containers in a virtual package, (1) a complete and balanced first food composition to provide a caloric maintenance diet containing calories that meet the energy requirements of maintenance of an animal, (2) a second balanced and complete feed composition to provide a caloric reduction diet containing about 40% to about 60% of the calories contained in the caloric maintenance diet, and (3) instructions for use food compositions, for use in a method to reduce the incidence of cancer treatment, cancer prevention, reduction of the incidence of cardiovascular diseases, treatment of cardiovascular diseases, prevention of cardiovascular diseases, prevention of type II diabetes, prevention of prediabetes, treatment of type I diabetes, treatment of type II diabetes or treatment of prediabetes in an animal, the method comprising: feeding the animal the caloric maintenance diet containing calories that meet the maintenance energy requirements of the animal during a caloric maintenance period; and feeding the animal the caloric reduction diet containing from about 40% to about 60% of the calories contained in the caloric maintenance diet during a caloric reduction period; in which the caloric maintenance period and the caloric reduction period are in a ratio of 4:3. 3. The method of claim 1 or the kit for use according to claim 2, wherein the caloric maintenance period is 4 days and the caloric reduction period is 3 days. 4. The method of claim 3 or the kit for use according to claim 3, wherein the 4 days and the 3 days are consecutive. 5. The method of claim 3 or the kit for use according to claim 3, wherein the 4 days and the 3 days are not consecutive. 6. The method of claim 1 or the kit for use according to claim 2, wherein feeding for the caloric maintenance period and feeding for the caloric reduction period are repeated over a period of at least 1 month. 7. The method of claim 1 or the kit for use according to claim 2, wherein feeding for the caloric maintenance period and feeding for the caloric reduction period are repeated over a period of at least 6 months. 8. The method of claim 1 or the kit for use according to claim 2, wherein the calorie reduction diet contains approximately 50 of the calories necessary to meet the daily maintenance energy requirement of the animal. 9. A non-therapeutic method of feeding an animal to impart a non-therapeutic health benefit to the animal, wherein the non-therapeutic health benefit is selected from the group consisting of: preserving lean body mass, preventing or minimizing the loss of lean body mass during weight loss by the animal, avoiding a reduction in energy metabolism by the animal, reducing the risk of the animal regaining weight after weight loss, maintaining ideal body weight and improving undesirable animal behaviors associated with reduced caloric intake, comprising the method: feeding the animal a diet without limiting caloric intake during an ad libitum feeding period; and feeding the animal a calorie-reduced diet containing about 40% to about 60% calories that meet the animal's maintenance energy requirements. during a period of calorie reduction; in which the ad libitum period and the caloric reduction period are in a ratio of approximately 4:3. 10. A kit comprising in separate containers in a single container or in separate containers in a virtual container, (1) a first complete and balanced food composition to provide a diet without limit of caloric intake, (2) a second complete food composition and balanced provide a calorie reduction diet containing from about 40% to about 60% calories that meet the maintenance energy requirements of an animal, and (3) instructions for using the feed compositions, for use in a method for reduce the incidence of cancer, treat cancer, cancer prevention, reduce the incidence of cardiovascular diseases, treatment of cardiovascular diseases, prevention of cardiovascular diseases, prevention of type II diabetes, prevention of prediabetes, treatment of type I diabetes , treatment of type II diabetes or treatment of prediabetes in an animal, the method comprising: feed the animal the diet with no limit on caloric intake during an ad libitum feeding period; and feeding the animal the caloric reduction diet containing from about 40% to about 60% calories that meet the maintenance energy requirements of the animal during a period of caloric reduction; in which the ad libitum period and the caloric reduction period are in a ratio of approximately 4:3 11. The method of claim 9 or the kit for use according to claim 10, wherein the ad libitum period is 4 days and the caloric reduction period is 3 days. 12. The method of claim 9 or the kit for use according to claim 10, wherein the ad libitum feeding period and the caloric reduction period are consecutive. 13. The method of claim 9 or the kit for use according to claim 10, wherein the feeding for the ad libitum period and the feeding for the caloric reduction period are repeated over a period of at least 1 month. 14. The method of claim 9 or the kit for use according to claim 10, wherein the feeding for the ad libitum period and the feeding for the caloric reduction period are repeated over a period of at least 6 months. 15. The method of claim 9 or the kit for use according to claim 10, wherein the calorie reduction diet contains approximately 50 of the calories necessary to meet the daily maintenance energy requirement of the animal.